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A Mechanochemical Switch to Control Radical Intermediates

Publications associées (37)

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Optimal enzyme utilization suggests that concentrations and thermodynamics determine binding mechanisms and enzyme saturations

Vassily Hatzimanikatis, Daniel Robert Weilandt, Asli Sahin

One of the main challenges hampering the development of kinetic models is the lack of kinetic parameters for many enzymatic reactions. Here, the authors introduce a framework to explore the catalytically optimal operating conditions of any complex enzyme m ...

NATURE PORTFOLIO2023

Hypervalent Iodine: New Reagents and Functionalization of Peptides

Eliott Hugo Joran Le Du

Alkynes are found in a multitude of natural or synthetic bioactive compounds. In addition to the capacity of these chemical motifs to impact the physicochemical properties of a molecule of interest, the well-established reactivity of alkynes makes them ...

EPFL2023

Investigation of Carboxylic Acid Isosteres and Prodrugs for Inhibition of the Human SIRT5 Lysine Deacylase Enzyme

Alexander Lund Nielsen

Sirtuin 5 (SIRT5) is a protein lysine deacylase enzyme that regulates diverse biology by hydrolyzing epsilon-N-carboxyacyllysine posttranslational modifications in the cell. Inhibition of SIRT5 has been linked to potential treatment of several cancers but ...

2022

Activation of aminocyclopropanes via radical intermediates

Jérôme Waser, Mingming Wang

Aminocyclopropanes are versatile building blocks for accessing high value-added nitrogen-containing products. To control ring-opening promoted by ring strain, the Lewis acid activation of donor-acceptor substituted systems is now well established. Over the ...

2022

New Strategies for the Functionalization of Alkenes Exploiting Tethering Chemistry and Ring Strain

Bastian Antoine Rodolphe Claude Muriel

Amino alcohols, cyclopropanes and nitriles are privileged structural motifs found in the scaffold of natural products and bioactive compounds. In addition, they are versatile building blocks in organic chemistry. The development of new and increasingly eff ...

EPFL2021

Development of remote C-H bond functionalization of redox-active alcohol derivatives and oxidative transformations under photoredox catalysis

Alexandre Julien Florent Leclair

The development of radical-based remote C(sp3)-H functionalizations of redox-active alcohol derivatives, oxidative cycloaddition and rearrangement transformations under visible light photocatalysis constitute the basis of this thesis.The first chapter desc ...

EPFL2021

Synthetic methodologies for C-C and C-N bond formation involving alkyl radicals

Guido Barzanò

C-C and C-N bonds are some of the most common structures in molecules ranging from drugs to catalysts and to food additives. Many coupling reactions were developed to form these types of bonds with excellent selectivity and good performance. Still, the syn ...

EPFL2020

Enzyme annotation for orphan and novel reactions using knowledge of substrate reactive sites

Vassily Hatzimanikatis, Ljubisa Miskovic, Noushin Hadadi, Marianne Seijo

Thousands of biochemical reactions with characterized activities are “orphan,” meaning they cannot be assigned to a specific enzyme, leaving gaps in metabolic pathways. Novel reactions predicted by pathway-generation tools also lack associated sequences, l ...

PNAS2019

The evolution of multiple active site configurations in a designed enzyme

Ganna Gryn'ova, Dusan Petrovic

Developments in computational chemistry, bioinformatics, and laboratory evolution have facilitated the de novo design and catalytic optimization of enzymes. Besides creating useful catalysts, the generation and iterative improvement of designed enzymes can ...

NATURE PUBLISHING GROUP2018

Design of novel enzyme-catalyzed reactions linked to protein sequences for finding enzyme engineering targets

Vassily Hatzimanikatis, Jasmin Maria Hafner, Homa Mohammadi Peyhani, Noushin Hadadi

A key challenge in metabolic engineering is to find and to improve biosynthetic pathways that lead to the cellular production of a given industrial, pharmaceutical or specialty chemical compound. In many cases, the enzymatic reactions required for bio-prod ...

2017